Characterization of the biological role of Opi1, a transcriptional repressor of phospholipid metabolism, in the regulation of the DNA damage signaling

Abstract

Chromatin can be damaged by several factors form endogenous or exogenous sources, which can lead to DNA breaks, replication fork stall and collapse and histone and other proteins modifications. The DNA damage responses (DDR) consist of several protein effectors that regulate several cellular processes with the ultimate goal to prevent genomic instability and loss of cell viability. The Opi1 protein (from Over Producer of Inositiol), a repressor of the transcription of genes involved in inositol biosynthesis, is involved in the DNA damage response by an unknown mechanism. It was observed that strains lacking Opi1, present MMS (methyl metanesulphonate) hipersensitivity. Interestingly, phosphoproteomic data have shown that Opi1 is extensively phosphorylated by the DDR kinase Mec1 (ATR in humans), suggesting a regulatory role upon Opi1. Therefore, this project has the objective to study the biological role of Opi1 during the DDR and also to investigate if Opi1 is regulated through phosphorylation by Mec1, and consequently if this kinase is an important regulator of inositol metabolism. (AU)